PROTEINS IN LEAD-INDUCED NUCLEAR INCLUSION BODIES

铅中毒诱导核小体，由铅和蛋白质组成， 许多动物包括人。这些机构是突出的肾小管 内衬细胞。 铅中毒的临床影响是众所周知的，但 核包涵体的功能和作用都不是 知道的 它们可能反映了一种调节过程， 可溶性铅 它们的形成在细胞培养物中被以下物质的抑制剂阻断： RNA和蛋白质合成，这表明诱导蛋白质是 涉案 包涵体含有一个突出的蛋白质， 在其他地方检测到，这表明它是诱导的， 被铅隔离 为了了解包涵体的形成和 功能，有必要将这些蛋白质的代谢与 铅暴露和研究蛋白质与铅的相互作用。 的 包涵体的化学性质严重限制了 他们的研究。 在相关合成中将使用细胞培养系统 包涵体蛋白质与铅接触。 此外，合成 同源mRNA将通过体外翻译测定来确定， 以确认铅诱导。 这些蛋白质结合的倾向 将通过将纯化的结合蛋白暴露于可溶性 放射性铅。 将制备单克隆抗体并用于 分析和纯化蛋白质，并表征其 细胞内定位。 互补DNA克隆将在 为了能够定量地研究基因活性的调节， 各种细胞和各种刺激下，如铅，其他金属， 其他创伤性影响，如热。 铅对细胞的影响 很难在分子水平上进行研究。 然而申请 最近开发的程序，以研究长期公认的核 包涵体为研究这一问题提供了独特的机会。

Lead poisoning induces nuclear bodies, composed of lead and protein, in many animals including man. These bodies are prominent in renal tubular lining cells. There are well known clinical effects of lead poisoning, but neither the function nor the effect of the nuclear inclusion bodies is known. They may reflect a regulated process which decreases the level of soluble lead. Their formation is blocked in cell culture by inhibitors of RNA and protein synthesis, suggesting that inducible proteins are involved. The inclusion bodies contain a prominent protein which has not been detected elsewhere, suggesting that it is either induced or sequestered by lead. In order to understand inclusion body formation and function, it is necessary to relate the metabolism of these proteins to lead exposure and to study the interactions of the proteins with lead. The chemical properties of the inclusion bodies impose severe restraints on their study. A cell culture system will be used in correlating synthesis of inclusion body proteins with lead exposure. Further, the synthesis of the cognate mRNA's will be determined by an in vitro translation assay in order to confirm induction by lead. The tendency of these proteins to bind lead will be studied by exposure of purified, bound protein to soluble radioactive lead. Monoclonal antibodies will be prepared and used for assaying and purifying the proteins and in characterizing their intracellular location(s). Complementary DNA clones will be isolated in order that regulation of gene activity can be studied quantitatively in various cells and under various stimuli such as lead, other metals, and other traumatic effects such as heat. The effects of lead on cells have been difficult to study at the molecular level. However, the application of recently developed procedures to a study of the long recognized nuclear inclusion bodies provides a unique opportunity to study this problem.